The maintenance of intestinal immune homeostasis involves the balanced interaction of bacterial microflora, gut epithelium and host innate immune cells. Deregulation of these immunological interactions can result in immune dysfunction and lead to overt inflammation typical of human inflammatory bowl disease (IBD), including ulcerative colitis (UC) and Crohn's disease. Although the cellular and molecular mechanisms of IBD are not fully understood, data indicate that chronic intestinal inflammation induced by inflammatory cytokines (e.g. IL-12) plays a pivotal role. These cytokines initiate the differentiation of pathogenic CD4+ T cells that are strongly involved in disease progression. Accordingly, studies show that regulation of these cells mitigates experimental colitis. Additionally, like IL-12, secreted IL-23 from activated dendritic cells (DCs) that utilize the IL-12p40 subunit is also implicated in the development of various autoimmune diseases, including IBD. The inflammatory nature of IL-23 has been attributed to induction of Th17. Furthermore, this cytokine also activates the production of inflammatory cytokines such as TNFα and IL-6 in DCs. Together, studies show that blocking the IL-12p40 subunit signaling significantly reduces inflammation, and indicate that both IL-12 and IL-23 participate in the inflammatory cascade causing IBD. In contrast to both of these cytokines, IL-10 exerts regulatory effects on the inflammatory signals, thereby modulating the immune response elicited by inflammatory cytokines.
Probiotic microbes can interact with the host's immune cells and specific probiotic Lactobacillus species may stimulate DCs to produce inflammatory cytokines (i.e. IL-12) and regulatory IL-10. Lactobacilli are normal inhabitants of the human gastrointestinal tract and major components of the natural microbiota in the small bowel. These bacteria are considered beneficial commensals and some species and strains are generally recognized as safe due to a long history of human consumption.
Further methods and compositions are needed in the art to improve the treatment of inflammatory gastrointestinal disorders, such as IBD.